result of muscle protein synthesis may range from 485 kcal/d
in a well-muscled young man to120 kcal/d in an active elderly
woman. These estimates are consistent with the observed increase
in REE during an infusion of amino acids at a rate known
to stimulate muscle protein synthesis (24). Extremes in muscle
mass, eg, young male body builders to frail elderly, would be
even greater. In terms of whole-body energy balance, a difference
in REE of 365 kcal/d, stemming from a difference in
muscle protein turnover, would lead to a gain or loss of 47 g fat
mass/d because 1 kg of fat stores 7700 kcal. If activity and diet
remained constant, this would mean a gain or loss of1.4 kg fat
mass/mo. This effect on energy balance is particularly striking
when it is realized that the estimate given above for the energy
expenditure associated with muscle protein turnover is likely an
underestimate, because protein breakdown also requires the hydrolysis
of ATP, and the energy released in this process is above
and beyond the contribution of muscle protein synthesis to energy
production. It is evident from these estimations that, when
a long-term perspective is considered, even relatively small differences
(eg, 10 kg) in muscle mass could have a significant
effect on energy balance. Every 10-kg difference in lean mass
translates to a difference in energy expenditure of 100 kcal/d,
assuming a constant rate of protein turnover. In considering the
magnitude of energy imbalances leading to obesity, it is reasonable
to view the situation over long periods of time, because
obesity often develops over months and even years.Adifference
in energy expenditure of 100 kcal/d translates to 4.7 kg fat
mass/y. Consequently, the maintenance of a large muscle mass
and consequent muscle protein turnover can contribute to the
prevention of obesity.
Regardless of the energetics of muscle protein turnover, obesity
can develop if energy intake is great enough. Obesity is
clinically characterized by a disproportionate increase in fat
mass. Less appreciated is the fact that muscle mass in obesity is
also increased (25). Although the energy expenditure associated
with larger muscle mass in obesity is insufficient to offset the
excessive energy intake, the expanded muscle mass can be capitalized
on to facilitate weight loss. It is evident from the calculations
presented above that a stimulation of muscle protein turnover
in the setting of increased muscle mass could have a
significant effect on REE and, thus, energy balance. This can
potentially be accomplished through nutrition, because increasing
amino acid availability increases muscle protein turnover
(26). Furthermore, the energy to provide the ATP for muscle
protein turnover is largely derived from the oxidation of fat,
because this is the preferred energy substrate of resting muscle
(27). Thus, when muscle protein synthesis was increased by
testosterone injection in hypogonadal elderly men, the increase
in lean body mass over time was accompanied by a decrease in fat
mass (28). Extending this notion to the situation of a hypocaloric
diet for weight loss, a high percentage of protein in the diet would
therefore be expected to effectively repartition nutrient deposition
from fat to muscle. Recent reports of improved body composition
during weight loss with high-protein, hypocaloric diets
support the notion of repartitioning of nutrient intake when protein
turnover is stimulated (29). It has yet to be determined
whether the same repartitioning occurs when the proportion of
protein intake is increased in the circumstance of energy balance
(ie, caloric intake caloric expenditure), but the same rationale
should apply.